Publications by authors named "Ana Soares"

341 Publications

As trials go by: Effects of 2-AFC item repetition on statistical learning performance.

Can J Exp Psychol 2022 Aug 4. Epub 2022 Aug 4.

Human Cognition Lab.

One of the most popular tasks used to test statistical learning (SL) involves asking participants to identify which of two stimuli, a triplet presented during the previous familiarization phase versus a new sequence made of the same stimuli never presented together, is more familiar based on the stream presented before, that is, to perform a two-alternative forced-choice (2-AFC) task. Despite the widespread use of this task, it has come under increasing criticism in current cognitive research due to psychometric flaws. A common practice to improve SL measurement involves increasing the number of 2-AFC trials by presenting the same items (triplets and foils) several times during the test phase. This work aimed to directly analyze the effect that this practice entails by examining how the proportion of correct discriminations of three-syllable nonsense words presented during the familiarization phase of an auditory triplet embedded task changed as the number of 2-AFC item repetitions increased. We also tested whether this effect was modulated by the predictability of the "words" embedded in the auditory streams (high and low) and the conditions under which they were presented to participants (implicit and explicit). Results showed that 2-AFC item repetitions had indeed detrimental effects on SL measurement, as indexed by a significant decrease in the proportion of correct discriminations as the number of items repetitions increased, both in the 2-AFC task performed under implicit and explicit conditions, although, in the first case, only for low-predictable "words." These findings recommend caution when using this strategy to improve SL measurement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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http://dx.doi.org/10.1037/cep0000290DOI Listing
August 2022

Genetic counseling and carrier screening in candidates for gamete donation at a Portuguese center.

JBRA Assist Reprod 2022 Aug 1. Epub 2022 Aug 1.

Serviço de Genética Médica, Centro de Genética Médica Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal.

Objective: Genetic counseling and carrier screening are part of the gamete donation process by healthy individuals. We aim to review the findings of genetic counseling and carrier screening of a cohort of candidates at our public gametes bank.

Methods: Thirty-four male and 64 female candidates had genetic counseling with a medical geneticist before donation. Of these, one female candidate voluntarily dropped-out. Thirty-four males and 63 females performed karyotype and screening for the more common pathogenic variants for CFTR-related cystic fibrosis and spinal muscular atrophy (SMN1) in the Portuguese population. In addition, all females also performed Fragile X expansion screening (FMR1). Thirty candidates with known or assumed African ancestry performed hemoglobinopathies screening.

Results: Six candidates were definitely or temporarily withheld from the donation process given their family or personal history that required further investigation. Of 97 candidates tested, 16.5% presented anomalous laboratory results (16/97): ten candidates were carriers for an autosomal recessive disorder - cystic fibrosis (5/97), sickle cell anemia (3/30), and spinal muscular atrophy (2/97). One female was an FMR1 pre-mutation carrier (1/63). One female candidate presented with triple X mosaicism: 47,XXX[2]/46,XX[50]. Two candidates presented with chromosomal instability of unknown origin. In one candidate, a mosaic for the Philadelphia chromosome was detected, revealing the diagnosis of chronic myeloid leukemia.

Conclusions: From a cohort of 97 candidates, 21.7% had a family/personal history or an anomalous laboratory result that required additional genetic counseling, stressing the importance of performing pre-donation genetic counseling in this population.
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http://dx.doi.org/10.5935/1518-0557.20220012DOI Listing
August 2022

Fluxes of the Amazon River plume nutrients and microbes into marine sponges.

Sci Total Environ 2022 Jul 19:157474. Epub 2022 Jul 19.

Laboratory of Microbiology, Biology Institute, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; Center of Technology - CT2, SAGE-COPPE, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. Electronic address:

Sponges have co-evolved with microbes for over 400 myr. Previous studies have demonstrated that sponges can be classified according to the abundance of microbes in their tissues as Low Microbial Abundance (LMA) and High Microbial Abundance (HMA). While LMA sponges rely mainly on water column microbes, HMA appear to rely much more on symbiotic fermentative and autotrophic microbes maintained in their tissues. However, it is unclear if this pattern holds when comparing different species of tropical sponges under extreme nutrient conditions and sediment loads in the water column, such as the Great Amazon Reef System (GARS), which covers an area of ~56,000 km off the Amazon River mouth. Sponges are the major GARS benthic components. However, these sponges' microbiome across the GARS is still unknown. Here, we investigated water quality, isotopic values (δC and δN), metagenomic and lipidomic profiles of sponges obtained from different sectors throughout the GARS. >180 million shotgun metagenomic reads were annotated, covering 22 sponge species. Isotopic and lipidomic analyses suggested LMA sponges rely on the Amazon River Plume for nutrition. HMA sponges (N = 15) had higher Roseiflexus and Nitrospira abundance, whereas LMA sponges (N = 7) had higher Prochlorococcus and Pelagibacter abundance. Functional data revealed that the LMA sponge microbiomes had greater number of sequences related to phages and prophages as well as electron transport and photophosphorylation which may be related to photosynthetic processes associated with the Prochlorococcus and Synechococcus found in the LMA. The higher phages abundance in LMA sponges could be related to these holobionts' reduced defense towards phage infection. Meanwhile, HMA sponge microbiomes had higher Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR abundance, which may be involved in defense against phage infection. This study sheds light on the nutrient fluxes and microbes from the Amazon River plume into the sponge holobionts.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157474DOI Listing
July 2022

Explicit Instructions Do Not Enhance Auditory Statistical Learning in Children With Developmental Language Disorder: Evidence From Event-Related Potentials.

Front Psychol 2022 30;13:905762. Epub 2022 Jun 30.

Center for Health Technology and Services Research ([email protected]), School of Health Sciences, University of Aveiro, Aveiro, Portugal.

A current issue in psycholinguistic research is whether the language difficulties exhibited by children with developmental language disorder [DLD, previously labeled specific language impairment (SLI)] are due to deficits in their abilities to pick up patterns in the sensory environment, an ability known as statistical learning (SL), and the extent to which explicit learning mechanisms can be used to compensate for those deficits. Studies designed to test the compensatory role of explicit learning mechanisms in children with DLD are, however, scarce, and the few conducted so far have led to inconsistent results. This work aimed to provide new insights into the role that explicit learning mechanisms might play on implicit learning deficits in children with DLD by resorting to a new approach. This approach involved not only the collection of event-related potentials (ERPs), while preschool children with DLD [relative to typical language developmental (TLD) controls] were exposed to a continuous auditory stream made of the repetition of three-syllable nonsense words but, importantly, the collection of ERPs when the same children performed analogous versions of the same auditory SL task first under incidental (implicit) and afterward under intentional (explicit) conditions. In each of these tasks, the level of predictability of the three-syllable nonsense words embedded in the speech streams was also manipulated (high vs. low) to mimic natural languages closely. At the end of both tasks' exposure phase, children performed a two-alternative forced-choice (2-AFC) task from which behavioral evidence of SL was obtained. Results from the 2-AFC tasks failed to show reliable signs of SL in both groups of children. The ERPs data showed, however, significant modulations in the N100 and N400 components, taken as neural signatures of word segmentation in the brain, even though a detailed analysis of the neural responses revealed that only children from the TLD group seem to have taken advantage of the previous knowledge to enhance SL functioning. These results suggest that children with DLD showed deficits both in implicit and explicit learning mechanisms, casting doubts on the efficiency of the interventions relying on explicit instructions to help children with DLD to overcome their language difficulties.
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http://dx.doi.org/10.3389/fpsyg.2022.905762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282164PMC
June 2022

Cinnamon Infusion Reduces Satiety and Increases Energy Intake: A Randomized Crossover Trial.

Ann Nutr Metab 2022 Jul 13. Epub 2022 Jul 13.

Background/aims: This study aimed to evaluate the effects of the intake of a single dose of cinnamon infusion on energy metabolism, appetite responses and food intake in healthy individuals.

Methods: This was an open randomized crossover clinical trial, with a minimum washout of seven days, which was conducted in which two standardized breakfasts were served randomly: one with cinnamon infusion (2g, Cinnamomum sp.) And one with water (control). The study included 21 healthy volunteers. Energy expenditure (EE), diet-induced thermogenesis (DIT), respiratory quotient (RQ), substrate oxidation and appetite responses were evaluated, as well as prospective food intake.

Results: Ingestion of cinnamon infusion did not alter EE, DIT, RQ or substrate oxidation. The incremental area under the curve for hunger, satiety and desire to eat did not differ between the treatment with cinnamon infusion and water, however, there was a reduction in the feeling of satiety (p=0.021) compared to the control treatment. The energy consumption of the first meal after treatment was higher (p=0.05) in the treatment with cinnamon infusion than in the control treatment. Regarding macronutrients or food intake throughout the day, there was no difference between treatments.

Conclusions: Although it did not affect energy metabolism, consuming a single dose of cinnamon infusion promoted less feeling of satiety and increased energy intake in the first meal after treatment. The study protocol was registered at the Brazilian Clinical Trials Registry Platform (RBR-5ftg3z).
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http://dx.doi.org/10.1159/000525949DOI Listing
July 2022

Role of chronotype in dietary intake, meal timing, and obesity: a systematic review.

Nutr Rev 2022 Jun 30. Epub 2022 Jun 30.

Graduate Program in Health Sciences, Faculty of Medicine, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.

Context: Recent studies show that dietary habits and obesity seem to be influenced by chronotype, which reflects an individual's preference for the timing of sleeping, eating, and activity in a 24-hour period.

Objective: This review aimed to analyze the association of chronotype with dietary habits, namely energy and macronutrient intakes, meal timing, and eating patterns, as well as with obesity.

Data Sources: PubMed/MEDLINE, LILACS, and Google Scholar databases were searched between 2004 and 2020. Study selection was performed by 2 authors independently; disagreements on eligibility of articles were resolved by a third author. After assessment of 12 060 abstracts, 43 studies (21 articles on obesity; 13 on food consumption, meal timing, and eating patterns; and 9 that addressed both obesity and dietary behavior) were included.

Data Extraction: A standard form was used to extract study design, country, number of participants, method of chronotype determination, and main findings.

Data Analysis: Approximately 95% of included studies showed an association between eveningness and at least 1 unhealthy eating habit. Morningness was associated with regular consumption of fresh and minimally processed foods. In addition, about 47% of studies showed a higher association between late types and obesity.

Conclusion: Late types are more likely to present unhealthy eating habits, such as eating late at night, skipping breakfast often, and eating processed/ultraprocessed foods, while early types are more likely to have healthy and protective habits, such as eating early and eating predominantly fresh/minimally processed foods. Intermediate types tend to have a pattern of health and eating more similar to early types than to late types. Late types are also more likely to present higher weight and body mass index than early or intermediate types.

Systematic Review Registration: PROSPERO registration no. CRD42021256078.
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http://dx.doi.org/10.1093/nutrit/nuac044DOI Listing
June 2022

Child maltreatment and substances use throughout adolescence and adulthood: Data from a Brazilian Birth Cohort.

Child Abuse Negl 2022 Sep 25;131:105766. Epub 2022 Jun 25.

Postgraduate Program in Epidemiology, Federal University of Pelotas, Marechal Deodoro Street, 1160-3rd floor, Pelotas, RS 96020-220, Brazil.

Background: Child maltreatment has been associated with substance use later in life, but few studies have used repeated measures.

Objective: To assess the association between child maltreatment and use of psychoactive substances from adolescence to early adulthood, and whether this differs by sex.

Participants And Setting: 3641 participants from the 1993 Pelotas Birth Cohort, Brazil.

Methods: Child maltreatment (psychological, physical and sexual abuse, and physical neglect) was assessed up to age 15 and use of psychoactive substances (smoking, harmful use of alcohol and use of illicit drugs) was assessed at ages 15, 18, and 22 years. Associations between child maltreatment and use of substances at each time point were analyzed using logistic regression, adjusted for confounders.

Results: Overall, child maltreatment was associated with substance use, and the strength of the associations decreased over time. E.g., the association between psychological abuse and harmful use of alcohol was OR 2.17 (95%CI 1.80, 2.62; p-value < 0.001) at 15 years, OR 1.61 (95%CI 1.31, 1.97; p-value < 0.001) at 18 years, and OR1.55 (95%CI 1.22, 1.96; p-value < 0.001) at 22 years. When sex differences were evident, stronger associations were observed among females. E.g., the association between physical abuse and smoking at 15 years was OR 3.49 (95%CI 2.17, 5.62) in females and OR 0.87 (95%CI 0.30, 2.52) in males (p-value for sex interaction = 0.041).

Conclusions: Child maltreatment was associated with psychoactive substance in adolescence and early adulthood. Strategies to prevent use of substances could benefit those who suffered maltreatment in childhood.
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http://dx.doi.org/10.1016/j.chiabu.2022.105766DOI Listing
September 2022

Mental Health and Social Connectedness During the COVID-19 Pandemic: An Analysis of Sports and E-Sports Players.

Front Psychol 2022 25;13:802653. Epub 2022 May 25.

Departamento de Psicologia, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil.

Recently, the pandemic context in which the world finds itself has inspired studies that sought to evaluate to mental health and the way people are relating to the purpose of understanding and promoting improvements psychological health. The epidemiological and public health literature shows that social connection protects and promotes mental health, being an important clinical tool for reducing anxiety, depression, and stress. Thinking in the broad sense of connection, that is, feeling and perceiving oneself connected with the environment, applied to the context of sport, it is suggested that social connection could be related to the interactions in the practice of sport. Although playing sports can promote mental health, there are few findings on the topic in the context of a pandemic and with physical sports and electronic sports (e-sports) players. In this sense, the present study aims to assess the extent to which social connection and mental health indicators are correlated in a sample of sports and e-sports players. The participants were 401 Brazilian physical sports ( = 199, 49.6%) and e-sports players ( = 202, 50.4%), mostly male (53.1%) and single (59.9%), who filled in the Social Connectedness Scale (SCS), the Depression, Anxiety and Stress Scale (DASS), and demographic questions. The results indicated that social connection was negatively correlated and also predict the anxiety ( = -0.37), depression ( = -0.54), and stress ( = -0.39). When comparing sports and e-sports players, a statistically significant difference was identified in the levels of social connection [(398) = -3.41; sports (SD) = 4.53 (1.14); e-sports (SD) = 4.14 (1.15)] and depression [(396) = 2.90; sports (SD) = 1.10 (0.89); e-sports (SD) = 0.85 (0.81)]. These findings can serve as a theoretical basis for the development of intervention programs (e.g., to guide managers regarding the social distancing rules that enable them to keep holding sports practices and events) and promoting discussions that focus on the analysis of aspects promoting psychological health in sports context (physical and e-sports).
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http://dx.doi.org/10.3389/fpsyg.2022.802653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180132PMC
May 2022

Effects of COVID-19 pandemic on stress level of residents and fellows during ophthalmology training.

Indian J Ophthalmol 2022 Jun;70(6):2170-2173

Department of Ophthalmology; Department of Research, Altino Ventura Foundation, Recife, Brazil.

Purpose: To evaluate the impact of coronavirus disease 2019 (COVID-19) on the mental health of residents and fellows in ophthalmology.

Methods: A questionnaire composed of 42 questions was applied to Brazilian residents and fellows in Ophthalmology. The questionnaire addressed the demographics of participants, their working conditions before and during the COVID-19 pandemic, and the Perceived Stress Scale (PSS-10).

Results: The study had a total of 271 participants in Ophthalmology training, from which 100 were fellows and 171 were residents. Before the pandemic, Ophthalmology residents and fellows had a higher workload (P < 0.001), and residents worked more hours than fellows (P = 0.001). During the pandemic, the workload of both residents and fellows decreased and equalized (P = 0.195). No correlation was found between the working hours during the pandemic and their stress level were observed (P = 0.760). Higher stress scores were identified in women ophthalmologists (P = 0.001) as well as in residents and fellows that had their surgical training interrupted during the pandemic (P < 0.001).

Conclusion: The stress level of residents and fellows during the COVID-19 pandemic was similar, however, those that had their surgical training interrupted during the pandemic presented higher level of stress. Female physicians also presented higher level of stress compared to male physicians.
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http://dx.doi.org/10.4103/ijo.IJO_401_22DOI Listing
June 2022

Editorial: Viruses and Epitranscriptomes: Regulation of Infection and Antiviral Response.

Front Cell Dev Biol 2022 9;10:917894. Epub 2022 May 9.

Department of Medical Sciences, Institute of Biomedicine-IBiMED, University of Aveiro, Aveiro, Portugal.

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http://dx.doi.org/10.3389/fcell.2022.917894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125315PMC
May 2022

Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells.

Front Mol Biosci 2022 2;9:809985. Epub 2022 May 2.

Department of Medical Sciences, Institute of Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal.

Serine tRNAs (tRNA) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNA abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNA(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNA(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2 dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNA(AGA) enhanced transformation potential , and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers.
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http://dx.doi.org/10.3389/fmolb.2022.809985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108184PMC
May 2022

Scenario building model to support the resilience planning of winemaking regions: The case of the Douro territory (Portugal).

Sci Total Environ 2022 Sep 12;838(Pt 1):155889. Epub 2022 May 12.

Centre of Mathematics, University of Minho, Portugal. Electronic address:

Today resilience paradigm is shared by both academic and political debates, and it is gradually being implemented into plans, programmes, and project's initiatives. In this context, wine regions, particularly those designated as UNESCO sites, show their robustness and vulnerabilities as Socio-Ecological Systems. The climate change impact is increasing the exposure of their aesthetic, cultural, economic, natural values to potential losses and therefore an effective response is required To build resilient strategies, Decision Makers are increasingly considering multidimensional models in planning and assessment processes. This paper continues a research work that develops an integrated evaluation framework constituted by Multicriteria Decision Analysis to calculate a Territorial Resilience Index, a dynamical model to predict future ecological scenarios and scenario building to define a resilient strategy for the Douro territory (Portugal). This paper focuses on scenario building which uses specific tools such as Social Network Analysis to identify and investigate the relationships between real actors and stakeholders, Wilson matrix to assess the degree of uncertainty and relevance of the strategies identified by a panel of specialists, and consistency matrix to evaluate the strategies consistency in achieving the Sustainable Development Goals and UNESCO requirements. The obtained protocol of guidelines and recommendations can support Decision Makers in the design of sustainable and resilient transformation, thereby assisting in the preservation of the UNESCO site.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155889DOI Listing
September 2022

Disclosing azole resistance mechanisms in resistant Candida glabrata strains encoding wild-type or gain-of-function CgPDR1 alleles through comparative genomics and transcriptomics.

G3 (Bethesda) 2022 Jul;12(7)

iBB, Institute for Bioengineering and Biosciences, Instituto Superior Técnico-Department of Bioengineering, Universidade de Lisboa, Lisboa 1049-001, Portugal.

The pathogenic yeast Candida glabrata is intrinsically resilient to azoles and rapidly acquires resistance to these antifungals, in vitro and in vivo. In most cases azole-resistant C. glabrata clinical strains encode hyperactive CgPdr1 variants, however, resistant strains encoding wild-type CgPDR1 alleles have also been isolated, although remaining to be disclosed the underlying resistance mechanism. In this study, we scrutinized the mechanisms underlying resistance to azoles of 8 resistant clinical C. glabrata strains, identified along the course of epidemiological surveys undertaken in Portugal. Seven of the strains were found to encode CgPdr1 gain-of-function variants (I392M, E555K, G558C, and I803T) with the substitutions I392M and I803T being herein characterized as hyper-activating mutations for the first time. While cells expressing the wild-type CgPDR1 allele required the mediator subunit Gal11A to enhance tolerance to fluconazole, this was dispensable for cells expressing the I803T variant indicating that the CgPdr1 interactome is shaped by different gain-of-function substitutions. Genomic and transcriptomic profiling of the sole azole-resistant C. glabrata isolate encoding a wild-type CgPDR1 allele (ISTB218) revealed that under fluconazole stress this strain over-expresses various genes described to provide protection against this antifungal, while also showing reduced expression of genes described to increase sensitivity to these drugs. The overall role in driving the azole-resistance phenotype of the ISTB218 C. glabrata isolate played by these changes in the transcriptome and genome of the ISTB218 isolate are discussed shedding light into mechanisms of resistance that go beyond the CgPdr1-signalling pathway and that may alone, or in combination, pave the way for the acquisition of resistance to azoles in vivo.
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http://dx.doi.org/10.1093/g3journal/jkac110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258547PMC
July 2022

Grapiprant or carprofen following ovariohysterectomy in the cat: analgesic efficacy, hematological, biochemical and urinalysis evaluation.

J Feline Med Surg 2022 Aug 9;24(8):e153-e162. Epub 2022 May 9.

Graduate Program in Veterinary Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Objectives: This study aimed to compare the analgesic effect between carprofen and grapiprant every 12 or 24 h on postoperative pain in cats undergoing ovariohysterectomy, in addition to the effects on the hematological, biochemical and urinalysis variables.

Methods: A total of 32 female cats were randomly divided into three groups, according to the treatment administered with the first dose given orally 90 mins before surgery, as follows: CAR (cats received 4 mg/kg carprofen, n = 11); GRA1 (cats received 2 mg/kg grapiprant, n = 10); and GRA2 (cats received 2 mg/kg grapiprant q12h, n = 11). Pain was assessed by UNESP-Botucatu Multidimensional Composite Pain Scale (UNESP) and Glasgow Feline Composite Measure Pain Scale (GLASGOW) for cats preoperatively (baseline) and at 1, 3, 6, 8, 12 and 24 h after extubation. Venous blood was collected at baseline, and 12 and 24 h after the administration of carprofen or grapiprant to perform a complete blood count (CBC), the percentage of Heinz bodies and serum biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, creatinine and urea). Urinalysis was performed at baseline and 24 h after extubation. Glucose levels were evaluated at baseline and 1 h postoperatively.

Results: Pain scores were not significantly different among groups in both scales, although pain was higher at 3 h in comparison with 24 h in all groups. In the GRA1 and GRA2 groups, 67% (14/21) of cats needed rescue analgesia compared with 18% (2/11) in the CAR group. Glucose increased from baseline to 1 h in the GRA1 and GRA2 groups. None of the CBC, serum biochemistry and urinalysis variables differed among groups.

Conclusions And Relevance: Grapiprant did not promote adequate analgesia during the first 3 h postoperatively in cats undergoing ovariohysterectomy compared with carprofen, and no benefits were observed by administering grapiprant every 12 h.
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http://dx.doi.org/10.1177/1098612X221097935DOI Listing
August 2022

Urethra Sparing With Target Motion Mitigation in Dose-Escalated Extreme Hypofractionated Prostate Cancer Radiotherapy: 7-Year Results From a Phase II Study.

Front Oncol 2022 29;12:863655. Epub 2022 Mar 29.

Department of Radiation Oncology, Champalimaud Centre for the Unknown, Lisbon, Portugal.

Purpose: To explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer.

Materials And Methods: Between June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed insertion of a 150-cm air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volumetric Modulated Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled D ≥45 Gy. Target motion ≥2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery.

Results: Patient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≥2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable-intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a Ga-labeled prostate-specific membrane antigen (Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≥3.

Conclusion: The rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/β ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation.
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http://dx.doi.org/10.3389/fonc.2022.863655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012148PMC
March 2022

Advances in the use of 3D colorectal cancer models for novel drug discovery.

Expert Opin Drug Discov 2022 Jun 27;17(6):569-580. Epub 2022 Mar 27.

i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.

Introduction: Colorectal cancer (CRC) is one of the most common and deadly tumors worldwide. CRC and models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. However, two-dimensional (2D) culture systems are considered too simple and do not represent the complex nature of the human tumor. However, three-dimensional (3D) models have emerged in recent years as more advanced and complex cell culture systems, able to closely resemble key features of human cancer tissues.

Areas Covered: The authors' review the currently established cell culture models and describe the advances in the development of 3D scaffold-free models to study CRC. The authors also discuss intestinal spheroids and organoids. As well as models for drug screening and metastatic CRC (mCRC).

Expert Opinion: The ideal CRC model is not yet established. Spheroid-based 3D models represent one of the most used approaches to recapitulate the tumor environment, overcoming some limitations of 2D models. Mouse and patient-derived organoids are more advanced models that can mimic more closely the characteristics and properties of CRC, with the possibility of including cells derived from patients with metastatic CRC.
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http://dx.doi.org/10.1080/17460441.2022.2056162DOI Listing
June 2022

Acute green tea infusion ingestion effect on energy metabolism, satiety sensation and food intake: A randomized crossover trial.

Clin Nutr ESPEN 2022 04 2;48:63-67. Epub 2022 Feb 2.

Food Science Post-Graduation Program, Pharmacy School, Universidade Federal de Minas Gerais, Antônio Carlos Avenue, 6627 Pampulha Campus, 31270-901, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Background: Green tea (Camellia sinensis L.) has an effect on energy metabolism, but little is known about its infusion intake impact on satiety responses.

Objective: This paper aimed at analyzing the effect of green tea on energy expenditure, satiety response, and food intake in humans.

Methods: The study involved 21 individuals (11 women, 10 men), and consisted of an open-label, crossover, randomized clinical trial (RBR-928HCW). Evaluation of subjects was performed as an acute study on two different days, after having a standardized breakfast accompanied by water or green tea. Indirect calorimetry was used to evaluate resting energy expenditure (REE), and a visual analogue scale to assess satiety. Food records were used to assess food intake along the day of the trial.

Results: Acute ingestion of green tea infusion with the standardized breakfast increased REE (p = 0.014) by 7.2 ± 11.7% at 240min compared to fasting (mean difference of REE between the time of 240min and fasting: +91 ± 157.6 kcal). No significant alterations were observed for substrate oxidation and respiratory quotient compared to the water treatment. A greater feeling of hunger was observed when volunteers ingested green tea (water -828.75 ± 494.2  cm min; green tea -549.8 ± 545.6  cm min; p = 0.026). No significant differences were observed regarding food intake energy and macronutrients between treatments.

Conclusions: Green tea increased energy expenditure and the subjective response of hunger in healthy individuals. This study is registered in the ReBEC Platform of the Brazilian Clinical Trials Registry (RBR-928HCW).
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http://dx.doi.org/10.1016/j.clnesp.2022.01.034DOI Listing
April 2022

The Role of MicroRNAs in Proteostasis Decline and Protein Aggregation during Brain and Skeletal Muscle Aging.

Int J Mol Sci 2022 Mar 17;23(6). Epub 2022 Mar 17.

Institute of Biomedicine-iBiMED, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.

Aging can be defined as the progressive deterioration of cellular, tissue, and organismal function over time. Alterations in protein homeostasis, also known as proteostasis, are a hallmark of aging that lead to proteome imbalances and protein aggregation, phenomena that also occur in age-related diseases. Among the various proteostasis regulators, microRNAs (miRNAs) have been reported to play important roles in the post-transcriptional control of genes involved in maintaining proteostasis during the lifespan in several organismal tissues. In this review, we consolidate recently published reports that demonstrate how miRNAs regulate fundamental proteostasis-related processes relevant to tissue aging, with emphasis on the two most studied tissues, brain tissue and skeletal muscle. We also explore an emerging perspective on the role of miRNA regulatory networks in age-related protein aggregation, a known hallmark of aging and age-related diseases, to elucidate potential miRNA candidates for anti-aging diagnostic and therapeutic targets.
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http://dx.doi.org/10.3390/ijms23063232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955204PMC
March 2022

Steroid-Quinoline Hybrids for Disruption and Reversion of Protein Aggregation Processes.

ACS Med Chem Lett 2022 Mar 14;13(3):443-448. Epub 2022 Feb 14.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal.

Reversing protein aggregation within cells may be an important tool to fight protein-misfolding disorders such as Alzheimer's, Parkinson's, and cardiovascular diseases. Here we report the design and synthesis of a family of steroid-quinoline hybrid compounds based on the framework combination approach. This set of hybrid compounds effectively inhibited Aβ1-42 self-aggregation by delaying the exponential growth phase and/or reducing the quantity of fibrils in the steady state. Their disaggregation efficacy was further demonstrated against preaggregated Aβ1-42 peptides in cellular assays upon their endocytosis by neuroblastoma cells, as they reverted both the number and the average area of fibrils back to basal levels. The antiaggregation effect of these hybrids was further tested and demonstrated in a cellular model of general protein aggregation expressing a protein aggregation fluorescent sensor. Together, our results show that the new cholesterol-quinoline hybrids possess wide and marked disaggregation capacities and are therefore promising templates for the development of new drugs to deal with conformational disorders.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919386PMC
March 2022

Learning Words While Listening to Syllables: Electrophysiological Correlates of Statistical Learning in Children and Adults.

Front Hum Neurosci 2022 23;16:805723. Epub 2022 Feb 23.

Department of Psychology, University of Santiago de Compostela, Santiago de Compostela, Spain.

From an early age, exposure to a spoken language has allowed us to implicitly capture the structure underlying the succession of speech sounds in that language and to segment it into meaningful units (words). Statistical learning (SL), the ability to pick up patterns in the sensory environment without intention or reinforcement, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language, including the discovery of word boundaries in the continuous acoustic stream. Although extensive evidence has been gathered from artificial languages experiments showing that children and adults are able to track the regularities embedded in the auditory input, as the probability of one syllable to follow another syllable in the speech stream, the developmental trajectory of this ability remains controversial. In this work, we have collected Event-Related Potentials (ERPs) while 5-year-old children and young adults (university students) were exposed to a speech stream made of the repetition of eight three-syllable nonsense words presenting different levels of predictability (high vs. low) to mimic closely what occurs in natural languages and to get new insights into the changes that the mechanisms underlying auditory statistical learning (aSL) might undergo through the development. The participants performed the aSL task first under implicit and, subsequently, under explicit conditions to further analyze if children take advantage of previous knowledge of the to-be-learned regularities to enhance SL, as observed with the adult participants. These findings would also contribute to extend our knowledge of the mechanisms available to assist SL at each developmental stage. Although behavioral signs of learning, even under explicit conditions, were only observed for the adult participants, ERP data showed evidence of online segmentation in the brain in both groups, as indexed by modulations in the N100 and N400 components. A detailed analysis of the neural data suggests, however, that adults and children rely on different mechanisms to assist the extraction of word-like units from the continuous speech stream, hence supporting the view that SL with auditory linguistic materials changes through development.
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http://dx.doi.org/10.3389/fnhum.2022.805723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905652PMC
February 2022

Physiological parameters related to oocyte nuclear differentiation for the improvement of IVM/IVF outcomes in women and cattle.

Reprod Fertil Dev 2021 Dec;34(2):27-35

Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy.

In vitro maturation (IVM) has been applied in numerous different contexts and strategies in humans and animals, but in both cases it represents a challenge still far from being overcome. Despite the large dataset produced over the last two decades on the mechanisms that govern antral follicular development and oocyte metabolism and differentiation, IVM outcomes are still unsatisfactory. This review specifically focuses on data concerning the potential consequences of using supraphysiological levels of FSH during IVM, as well as on the regulation of oocyte chromatin dynamics and its utility as a potential marker of oocyte developmental competence. Taken together, the data revisited herein indicate that a significant improvement in IVM efficacy may be provided by the integration of pre-OPU patient-specific protocols preparing the oocyte population for IVM and more physiological culture systems mimicking more precisely the follicular environment that would be experienced by the recovered oocytes until completion of metaphase II.
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http://dx.doi.org/10.1071/RD21278DOI Listing
December 2021

Impaired catabolism of free oligosaccharides due to MAN2C1 variants causes a neurodevelopmental disorder.

Am J Hum Genet 2022 02 18;109(2):345-360. Epub 2022 Jan 18.

Univ. Lille, CNRS, UMR 8576-UGSF-Unit. de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France. Electronic address:

Free oligosaccharides (fOSs) are soluble oligosaccharide species generated during N-glycosylation of proteins. Although little is known about fOS metabolism, the recent identification of NGLY1 deficiency, a congenital disorder of deglycosylation (CDDG) caused by loss of function of an enzyme involved in fOS metabolism, has elicited increased interest in fOS processing. The catabolism of fOSs has been linked to the activity of a specific cytosolic mannosidase, MAN2C1, which cleaves α1,2-, α1,3-, and α1,6-mannose residues. In this study, we report the clinical, biochemical, and molecular features of six individuals, including two fetuses, with bi-allelic pathogenic variants in MAN2C1; the individuals are from four different families. These individuals exhibit dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Complementation experiments with isogenic MAN2C1-KO HAP1 cells confirm the pathogenicity of three of the identified MAN2C1 variants. We further demonstrate that MAN2C1 variants lead to accumulation and delay in the processing of fOSs in proband-derived cells. These results emphasize the involvement of MAN2C1 in human neurodevelopmental disease and the importance of fOS catabolism.
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http://dx.doi.org/10.1016/j.ajhg.2021.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874227PMC
February 2022

Is a negative correlation between sTNFR1 and TNF in patients with chronic Chagas disease the key to clinical progression?

Immunobiology 2022 01 17;227(1):152166. Epub 2021 Dec 17.

Fundação Oswaldo Cruz-Fiocruz, Instituto Aggeu Magalhães, Laboratório de Imunoparasitologia, Recife, PE, Brazil. Electronic address:

Soluble TNF receptors (sTNFR1 and sTNFR2) are natural endogenous inhibitors of TNF and are elevated in inflammatory, autoimmune, and chronic degenerative diseases. In Chagas disease, pleiotropic cytokine TNF is considered key in immunopathology. Thus, we aimed to evaluate the levels of TNF, sTNFR1, and sTNFR2 in the serum of patients with chronic Chagas disease. TNF and its soluble receptors were quantified using Cytometric Bead Array in the serum of 132 patients, of which 51 had the indeterminate form (IND), 39 the mild cardiac form (CARD 1), 42 the severe cardiac form (CARD 2), and 20 non-infected individuals (NI). The results indicate that the soluble receptors may regulate TNF in Chagas disease, as their leves were higher in T. cruzi-infected individuals when compared to non-infected individuals. We found a moderate negative correlation between sTNFR1 and TNF in individuals with the IND form, suggesting a relationship with non-progression to more severe forms, such as heart disease. sTNFR1 and sTNFR2 were increased in all clinical forms, but with a moderate positive correlation in more severe patients (r = 0.50 and p = 0.0005). TNF levels showed no statistical differences in the groups of patients. These findings suggest the importance of the endogenous balance of the levels of soluble TNF receptors in the protection and balance in patients with chronic Chagas disease, besides revealing the immunological complexity in chronic T. cruzi-infected individuals.
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http://dx.doi.org/10.1016/j.imbio.2021.152166DOI Listing
January 2022

Corrigendum to "Interface analysis after fatigue loading of adhesively luted bundled fiber posts to human root canal dentin". J. Mech. Behav. Biomed. Mater.; 119 (2021) 104385.

J Mech Behav Biomed Mater 2022 Feb 17;126:105045. Epub 2021 Dec 17.

Dept. of Operative and Preventive Dentistry, Charité - Universitätsmedizin Berlin, Aßmannshauserstraße 4-6, 14197, Berlin, Germany.

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http://dx.doi.org/10.1016/j.jmbbm.2021.105045DOI Listing
February 2022

Isolated abducens nerve palsy associated with coronavirus disease: an 8-month follow-up.

Arq Bras Oftalmol 2021 Nov 29. Epub 2021 Nov 29.

Department of Ophthalmology, Fundação Altino Ventura, Recife, PE, Brazil.

We report the case of a previously healthy 48-year-old man who developed an isolated abducens nerve palsy 18 days after presenting with coronavirus disease (COVID-19) confirmed by reverse transcriptase polymerase chain reaction. His main complaint at arrival was double vision. Ocular examination revealed a sixth cranial nerve palsy in the left eye. The incomitant esotropia at arrival was 30 prism diopters. Abduction was markedly limited, while adduction was normal in the left eye. The patient underwent complete clinical, neurological, and neuroimaging investigations, including cerebrospinal fluid sample analysis to rule out infectious causes. A conservative approach with orthoptic therapy and Fresnel prism was opted. Eight months after the onset of COVID-19, regression of the strabismus was observed, and the patient reported complete recovery of the diplopia. This case suggests that isolated abducens nerve palsy caused by severe acute respiratory syndrome coronavirus 2 infection may improve with a conservative approach.
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http://dx.doi.org/10.5935/0004-2749.20220063DOI Listing
November 2021

FTIR Spectroscopy as a Tool to Study Age-Related Changes in Cardiac and Skeletal Muscle of Female C57BL/6J Mice.

Molecules 2021 Oct 23;26(21). Epub 2021 Oct 23.

iBiMED, Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Agra do Crasto, 3810-193 Aveiro, Portugal.

Studying aging is important to further understand the molecular mechanisms underlying this physiological process and, ideally, to identify a panel of aging biomarkers. Animals, in particular mice, are often used in aging studies, since they mimic important features of human aging, age quickly, and are easy to manipulate. The present work describes the use of Fourier Transform Infrared (FTIR) spectroscopy to identify an age-related spectroscopic profile of the cardiac and skeletal muscle tissues of C57BL/6J female mice. We acquired ATR-FTIR spectra of cardiac and skeletal muscle at four different ages: 6; 12; 17 and 24 months (10 samples at each age) and analyzed the data using multivariate statistical tools (PCA and PLS) and peak intensity analyses. The results suggest deep changes in protein secondary structure in 24-month-old mice compared to both tissues in 6-month-old mice. Oligomeric structures decreased with age in both tissues, while intermolecular β-sheet structures increased with aging in cardiac muscle but not in skeletal muscle. Despite FTIR spectroscopy being unable to identify the proteins responsible for these conformational changes, this study gives insights into the potential of FTIR to monitor the aging process and identify an age-specific spectroscopic signature.
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http://dx.doi.org/10.3390/molecules26216410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587752PMC
October 2021

The Sisal Virome: Uncovering the Viral Diversity of Varieties Reveals New and Organ-Specific Viruses.

Microorganisms 2021 Aug 10;9(8). Epub 2021 Aug 10.

Center of Biotechnology and Genetics, Department of Biological Science, Universidade Estadual de Santa Cruz, Ilhéus 45662-900, Brazil.

Sisal is a common name for different plant varieties in the genus (especially ) used for high-quality natural leaf fiber extraction. Despite the economic value of these plants, we still lack information about the diversity of viruses (virome) in non- species from the genus . In this work, by associating RNA and DNA deep sequencing we were able to identify 25 putative viral species infecting and hybrid 11648, including one strain of (CPMMV) and 24 elements likely representing new viruses. Phylogenetic analysis indicated they belong to at least six viral families: Alphaflexiviridae, Betaflexiviridae, Botourmiaviridae, Closteroviridae, Partitiviridae, Virgaviridae, and three distinct unclassified groups. We observed higher viral taxa richness in roots when compared to leaves and stems. Furthermore, leaves and stems are very similar diversity-wise, with a lower number of taxa and dominance of a single viral species. Finally, approximately 50% of the identified viruses were found in all Agave organs investigated, which suggests that they likely produce a systemic infection. This is the first metatranscriptomics study focused on viral identification in species from the genus . Despite having analyzed symptomless individuals, we identified several viruses supposedly infecting species, including organ-specific and systemic species. Surprisingly, some of these putative viruses are probably infecting microorganisms composing the plant microbiota. Altogether, our results reinforce the importance of unbiased strategies for the identification and monitoring of viruses in plant species, including those with asymptomatic phenotypes.
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http://dx.doi.org/10.3390/microorganisms9081704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400513PMC
August 2021

Natural and Historical Heritage of the Lisbon Botanical Gardens: An Integrative Approach with Tree Collections.

Plants (Basel) 2021 Jul 4;10(7). Epub 2021 Jul 4.

Linking Landscape, Environment, Agriculture and Food (LEAF), Instituto Superior de Agronomia (ISA), Universidade de Lisboa, Tapada da Ajuda, 1340-017 Lisboa, Portugal.

Botanical gardens have long contributed to plant science and have played a leading role in ex situ conservation, namely of threatened tree species. Focusing on the three botanical gardens of Lisbon (i.e., Botanical Garden of Ajuda-JBA, Lisbon Botanical Garden-JBL, and Tropical Botanical Garden-JBT), this study aims to reveal their natural heritage and to understand the historical motivations for their creation. Our results showed that these gardens contain a total of 2551 tree specimens, corresponding to 462 taxa, within 80 plant families. Of these, 85 taxa are found in the three gardens, and more than half of the taxa are hosted in JBL (334 taxa), whereas 230 and 201 taxa were recorded in JBT and JBA, respectively. The motivations for the creation of each garden are reflected in the different geographic origins of the trees they host in their living collections. The Palearctic species are dominant in JBA and JBL, and Tropical trees prevail in JBT. With more than 250 years of history, these gardens hold an invaluable natural and historical heritage, with their living collections providing valuable sources of information for the conservation of threatened plant species, at local and global scales.
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http://dx.doi.org/10.3390/plants10071367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309379PMC
July 2021

The mechanisms of struvite biomineralization in municipal wastewater.

Sci Total Environ 2021 Dec 24;799:149261. Epub 2021 Jul 24.

Cranfield Water Science Institute, Cranfield University, Bedfordshire MK43 0AL, UK. Electronic address:

The mechanisms of struvite production by biomineralization were investigated for five microorganisms (Bacillus pumilus, Brevibacterium antiquum, Myxococcus xanthus, Halobacterium salinarum and Idiomarina loihiensis) in municipal wastewater. The microbial exponential phase of growth occurred within the first 48 h of incubation, with growth rates varying from 0.02-0.08 1/h. These five microorganisms removed 23-27 mg/L (66-79%) of ortho-phosphate from wastewater, which was recovered as biological struvite (i.e., bio-struvite) identified by morphological, X-ray diffraction and elemental analysis. Bio-struvite crystals occurred in a low extracellular supersaturation index (0.6-0.8 units). Bio-struvite formation in B. pumilus M. xanthus, H. salinarum cultures was linked to biologically induced mineralization. Whereas B. antiquum and I. loihiensis produced bio-struvite through biologically controlled mineralization mechanism because the crystals presented homogeneity in morphology and size, and intracellular vesicle-like cell structures were observed enclosing electron-dense granules/materials. Nutrient recovery through biomineralization has potential application in wastewater streams promoting circularity within the wastewater industry.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149261DOI Listing
December 2021
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